Pharmacological studies suggest that a dysfunction of the dopamine D2 receptor system is involved in schizophrenia. At present, it is not known what elements of this system, if any, are involved in the development of this disease. Possible abnormalities include, but are not limited to, expression of the dopamine D2 receptor, structural alterations at the gene level, post-translational modifications, and signal transduction. It has been suggested that subclasses of the D2 receptor with different abilities to recognize neuroleptic drugs may exist in different brain regions. Therefore, elucidation of the structure and expression of the D2 gene encode, will be important in understanding the molecular mechanisms underlying schizophrenia. The specific aims of this project are: (1) the determination of the structure of the human genes encoding the D2 receptor subtypes, (2) the development of probes to study the expression of these subtypes in brain, (3) the detection of any structural alterations of these genes associated with schizophrenia, and (4) the preparation of antisera specific for each D2 subtype. This will enable us to study the topographical distribution, expression, metabolism, and post-translational modifications of the various D2 receptor subtypes. These experiments will help in defining the role of the D2 receptor system in schizophrenia.